Elevated levels of serum angiopoietin-1, IL-17, osteopontin and CXCL-9 as markers of vascular inflammation in newly diagnosed PMR.

Abstract

GCA and PMR are commonly overlapping diseases. Biomarkers for detecting vascular inflammation in PMR patients are lacking. We aimed to determine the diagnostic value of serum levels of angiopoietin-1, angiopoietin-2, interleukin-6, interleukin-17A, interleukin-23, CXCL-9 and osteopontin (OPN) in identifying vascular inflammation in PMR. This was a multicentre prospective longitudinal study at Tallaght University Hospital (TUH) and St James Hospital (SJH), Dublin recruiting consecutive new patients. Serum levels of biomarkers were measured using the BioTechne ELISA assay kits following manufacturer protocols. Patients had standardized vascular ultrasound (US) of bilateral temporal and axillary arteries to identify vascular inflammation. Samples were collected from 53 PMR, 13 subclinical GCA in PMR (sGCA) and 59 GCA patients. GCA serum was significantly different from PMR; with higher levels of angiopoietin-1 (P < 0.001), angiopoietin-2 (P < 0.001), CXCL-9 (P < 0.001), osteopontin (P < 0.001), IL-6 (P = 0.02) and IL-17 (P < 0.001). Angiopoietin-1, IL-17, osteopontin (P < 0.001) and CXCL-9 (P = 0.004) were all significantly elevated in sGCA in PMR compared with pure PMR at baseline. IL-23, angiopoietin-2 or IL-6 was not significantly different in sGCA in PMR compared with pure PMR. ROC analysis produced AUC of 0.801 for angiopoietin-1 (sensitivity 84.6; specificity 70%), 0.892 for IL-17 (sensitivity 84.6%; specificity 79.2), 0.814 for osteopontin (sensitivity 84.5%; specificity 79.2%) and 0.892 for CXCL-9 (sensitivity 92.3%; specificity 62.3%). sGCA in PMR has a biomarker signature that more closely resembles GCA than PMR. Baseline levels of angiopoietin-1, IL-17, osteopontin and CXCL-9 may help identify PMR patients with vascular inflammation. These may be a useful screening tool to identify PMR patients that would benefit from further work-up.